Giving a pre-hospital shot of adrenaline, also known as epinephrine, to someone with cardiac arrest may help restore circulation in the short term, but could do them harm in the long term, according to a large new study from Japan published in JAMA on Wednesday that suggests it may be a case of saving the heart at the cost of the brain.

When someone has a cardiac arrest, their heart stops pumping blood, and if they don’t receive cardiopulmonary resuscitation (CPR) within minutes, they will probably die. When emergency services personnel attend such a casualty, they sometimes give them a shot of epinephrine to help get the heart started, before they get to hospital.

But researchers Dr Akihito Hagihara, of the Department of Health Services Management and Policy at Kyushu University Graduate School of Medicine, and colleagues, write in their background information that the effectiveness of epinephrine use before hospital arrival has not been established.

They examined registry data in Japan from 2005 to 2008 on 417,188 adults aged 18 and over who experienced out-of-hospital cardiac arrest before emergency services personnel arrived, and who were treated by the emergency services and then taken to hospital.

They assessed the relationship between pre-hospital use of epinephrine and several outcome measures: such as return of circulation before arriving at the hospital; survival at 1 month after cardiac arrest; and survival with and without brain damage or neurological problems.

They found that while use of epinephrine was linked to a higher chance of having circulation restored, within a month, those same patients were more likely to have died, or be left with brain damage or neurological problems.

Brain damage can occur after cardiac arrest because of lack of blood to the brain.

The researchers found that circulation returned in 18.5% of patients who received epinephrine before reaching the hospital, and in only 5.7% who did not.

But, the chances of being alive one month after cardiac arrest were a significant 54% less (adjusted odds ratio 0.46) in the patients who received pre-hospital epinephrine, who were also 68% significantly less likely to survive without some form of brain damage or neurological problems one month after.

These results were still significant when the researchers took into account possible influencing factors, such as whether CPR was given by a bystander or a paramedic, how long it was given for, and other differences between patients.

The researchers concluded that in Japan, among patients with out-of-hospital cardiac arrest, “use of prehospital epinephrine was significantly associated with increased chance of return of spontaneous circulation before hospital arrival but decreased chance of survival and good functional outcomes 1 month after the event.”

In an accompanying editorial, Dr Clifton Callaway, from the University of Pittsburgh, discusses the evidence about epinephrine use during CPR.

He says patients are more concerned about getting home intact than getting to the hospital with a beating heart.

You are more likely to get the heart beating again if you give it a dose of epinephrine, but the concern is always there, that it could harm other organs, he notes.

The researchers point out there are some weaknesses in their study: for instance they couldn’t take into account differences in hospital treatment, and whether, for instance, patients who didn’t receive it before arrival, were given epinephrine in the hospital.

Also, because of differences between what happens in Japan and elsewhere, it is not clear to what extent you can generalize these findings to other countries.

For instance, in Japan it is customary to give patients only one shot of epinephrine, whereas in the US, they are more likely to keep giving it every few minutes until the heart starts beating again.

Nevertheless, Callaway says the findings warrant further, more rigorous investigation. For instance, there could be a study where cardiac arrest patients are randomly assigned to receive epinephrine or not, and then followed for long term results.

Written by Catharine Paddock PhD